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Biomedical subjects

R Solà

Publications and source records attributed to R Solà.

At least 19 recordsLinked to original sources

IL-1beta induces VEGF, independently of PGE2 induction, mainly through the PI3-K/mTOR pathway in renal mesangial cells.

Vascular endothelial growth factor (VEGF) could play a relevant role in angiogenesis associated with chronic allograft nephropathy. Interleukin-1beta (IL-1beta) has a key role in inflammatory response. It induces prostaglandin (PG) E2, which is involved in VEGF release by some normal and tumor cells. In the present work, we studied the effect of IL-1beta on VEGF release by rat mesangial cells, the transduction signal, and whether or not PGE2 is involved in this effect. IL-1beta induced a time-dependent formation of VEGF (analyzed by enzyme-linked immunosorbent assay) and PGE2 (analyzed by enzyme immunoassay). The latter correlated with microsomal-PGE-synthase (mPGES)-1 expression rather than with cyclooxygenase (COX)-2 in terms of protein, determined by Western blotting. No effect of IL-1beta on COX-1, cytosolic PGES, or mPGES-2 expression was observed. Indomethacin exerted a nonsignificant effect on IL-1beta-induced VEGF, and exogenously added PGE2 exhibited a nonsignificant stimulatory effect on VEGF formation. SB 203580, a p38 mitogen-activated protein kinase inhibitor, weakly inhibited the induction of VEGF by IL-1beta in a concentration-dependent manner, whereas LY 294002, a phosphoinoside 3-kinase (PI3-K) inhibitor, and rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, strongly inhibited both IL-1beta- and tumor necrosis factor-alpha-induced VEGF formation in a concentration-dependent manner. Rapamycin also decreased glomerular VEGF levels in the anti-Thy1.1 model of experimental glomerulonephritis. In conclusion, the PI3-K-mTOR pathway seems to be essential in cytokine-induced release of VEGF in mesangial cells.

Animals↗

Assessment of the arteries in living kidney donors: correlation of magnetic resonance angiography with intraoperative findings.

Comprehensive imaging evaluation of kidney donor anatomy is crucial for selecting candidates for living kidney transplantation and for determining the surgical technique to procure the renal graft. In 76 living renal donors we compared the results of preoperative magnetic resonance angiography (MRA) with the intraoperative findings of arterial anatomy. Donors were evaluated for the number of main renal arteries and the presence of any polar arteries. A total of 80 main renal arteries and five polar arteries were observed at MRA. At surgery, 90 main renal arteries and eight polar arteries were identified. MRA demonstrated a sensitivity, specificity, and overall accuracy of 18%, 98%, and 87%, respectively, for main arteries and 25%, 96%, and 88% for polar arteries. Eleven (14.5%) kidneys displayed more than one main artery and MRA only detected two cases. Eight kidneys had polar arteries and MRA only detected two cases. MRA is a reliable method for presurgical evaluation of renal arteries in potential donors, providing valuable information required by the surgeon. But, as the technique misses small-diameter vessels, it cannot be recommended as the sole diagnostic tool in unclear cases.

Adult↗

Cardiovascular risk factors in diabetic patients with renal transplants.

There is a progressive increase in cardiovascular events post-renal transplantation and diabetes mellitus (DM) is one of the major cardiovascular risk factors. The objective of this study was to analyze the prevalence of cardiovascular risk factors and nonfatal cardiovascular events among renal transplant recipients, according to the status of their carbohydrate metabolism. We studied 214 renal transplant recipients, among whom 18% diabetic and 82% were nondiabetic. The 16% prevalence of cardiovascular events were higher among the posttransplantation DM (PTDM) group (33%) compared with the other groups, 19% in pre-renal transplantation DM, 17% in altered baseline glycemia, and 13% in normal patients. Diabetic renal transplant recipients showed a greater prevalence of pretransplantation ischemic cardiopathy when they were older and had a higher pretransplantation body mass index (BMI) a heavier smoking habit, significantly increased microinflammation markers, and a greater need for antihypertensive and hypolipidemic treatment. Renal transplant recipients with altered baseline glycemia show greater BMI after transplantation, as well as higher Hb1Ac than patients with normoglycemia.

Blood Pressure↗

Relation between pp65 antigenemia, RT-PCR and viruria for cytomegalovirus detection in kidney transplant recipients.

INTRODUCTION: We compared the efficiency of detection using pp65 antigenemia, reverse transcription-polymerase chain reaction (RT-PCR), and viruria for the diagnosis of cytomegalovirus (CMV) infections after kidney transplantation. PATIENTS AND METHODS: We evaluated 40 renal transplant recipients between weeks 5 and 12 after transplantation, including 179 blood and 181 urine specimens. RESULTS: All positive samples by antigenemia were also positive by PCR. However, in 52 cases only PCR was positive (kappa = 0.134 [P < .001]). Viruria was positive in 66 cases, but only 26 were CMV PCR positive. In 34 cases, viruria was negative and PCR positive (P = .192). CONCLUSION: Detection of DNA in serum is a more sensitive method than antigenemia for the diagnosis of CMV infection. Viruria was not related to the presence of CMV in blood.

Antigens, Viral↗

Results and complications of 50 laparoscopic nephrectomies for live donor renal transplantation.

Living donors represent 30% of kidneys for renal transplantation. Laparoscopic nephrectomy is the best surgical procedure due to its clear advantages: low morbidity, less blood transfusion requirements, and shorter donor hospitalization. From March 2002 to August 2004, we performed 50 laparoscopic nephrectomies for transplantation to recipients who were prescribed tacrolimus (0.1 mg/kg bid), mycophenolate mofetil (1 gr bid), and prednisone (0.5-1 mg/kg per day PO from 48 hours before transplantation). Mean surgery time was 170 minutes (120-260); warm ischemia time, 3.1 minutes (1.5-10); and cold ischemia time, 1.27 hours (0.85-4). Mean bleeding was 270 cc (100-900), and mean donor hospitalization was 5.5 days (3-9). Four cases required conversion of the laparoscopic procedure to open surgery because of bleeding. Seventy-two hours posttransplantation, the mean plasma creatinine was 170 micromol/L. None of the patients suffered delayed graft function. Eighteen percent experienced acute rejection episodes. Donor and recipient survivals were 100% at 1 year, and graft survival, 94% (kidney losses were due to acute rejection, severe acute pancreatitis, and surgical complications).

Employment↗

Post-renal transplantation weight gain: its causes and its consequences.

OBJECTIVE: A tendency to increased body mass index (BMI) occurs after renal transplantation. The objective of this study was to analyze the causes and consequences of this weight gain. METHODS: Two hundred twelve renal transplant recipients were divided into 3 groups according to the evolution of their BMI: BMI loss (group 1); BMI increase <10% (group 2); and BMI increase >10% (group 3). RESULTS: The mean BMI gain was 6.2%, weight gain was 3.9 kg, and BMI gain was 1.4 kg/m(2). The patients in group 3 were younger, but there were no other significant differences in gender, preoperative diabetes, acute rejection, or prior BMI. Blood pressure was similar in all 3 groups, but more group 3 patients needed antihypertensive treatment. A progressive increase in total and low-density lipoprotein (LDL)-cholesterol was also observed as patients showed increased BMI. No differences were observed regarding carbohydrate metabolism. Groups 1 and 3 showed a more unfavorable micro-inflammatory profile. The creatinine clearance level was better in group 3 compared with group 1. We found no differences regarding the number of nonfatal postoperative cardiovascular events.

Adult↗

Determining factors of the response to hyperhomocysteinemia treatment in renal transplant patients.

Hyperhomocysteinemia (hyperHcy) is a risk factor for cardiovascular disease. The benefits of lowering homocysteinemia (Hcy) in renal transplant recipients through vitamin treatment are not clearly understood. The objective of this study was to establish the demographic, renal, Hcy metabolism, and microinflammation factors that determined the response to folic acid and vitamin B complex treatment in stable patients with renal transplants and hyperHcy. We studied 65 renal transplant patients with baseline hyperHcy. The mean baseline Hcy level of these patients was 22.5 micromol/L. Following treatment it fell to 14.5 micromol/L, an overall reduction of 35.5%. Forty-one patients (63%) were classified as responders; the remainder (37%), nonresponders. A bivariance analysis suggested the only significant differences between responding and nonresponding patients were the pre-treatment Hcy level and the renal function level.

Adult↗

Factors involved in baseline hyperhomocysteinemia in renal transplantation.

Hyperhomocysteinemia (hyperHcy) is one cardiovascular risk. The objective of this study was to establish the prevalence demographic, and clinical and analytical factors related to hyperhomocysteinemia among renal transplant patients. The mean Hcy level was 17.3 micromol/L; the prevalence of hyperHcy was 61.2%. The population was categorized as hyperHcy and normal-homocysteinemia (Hcy) patients. Those subjects with hyperHcy were mostly men, with lower intraerythrocyte folate and vitamin B(12) levels, higher fibrinogen levels, and poorer renal function. Multivariate evaluation showed that creatinine clearance, plasma intraerythrocyte folate and vitamin B(12) levels, and plasma fibrinogen levels were independently associated with Hcy levels. Even though the Hcy level was slightly higher among patients who suffered a posttransplantation cardiovascular event, this was statistically significant.

Adult↗

Clinical usefulness of total hepatitis C virus core antigen quantification to monitor the response to treatment with peginterferon alpha-2a plus ribavirin*.

SUMMARY: Early virological response may predict outcome following treatment with peginterferon alpha-2a and ribavirin in patients chronically infected with hepatitis C virus (HCV). As total HCV core antigen may constitute an alternative direct marker to HCV RNA for assessing the levels of viraemia in such patients, we evaluated the correlation between HCV core antigen and HCV RNA, and whether HCV core antigen at baseline, 4 and 12 weeks after treatment could predict sustained virological response (SVR) to combined therapy, in comparison with HCV RNA. A total of 290 serum samples from 58 previously treatment naïve chronic HCV patients were examined for HCV core antigen and HCV-RNA by means of quantitative HCV RNA when receiving combination therapy for the first time. SVR was significantly associated with basal HCV core antigen but not with HCV RNA. There was a good correlation between HCV core antigen and HCV RNA (r(2) = 0.781). The negative predictive value of HCV core antigen testing in predicting nonresponse at weeks 4 and 12 were 75 and 100%, and for undetectable or a 2-log drop in HCV RNA were 69.6 and 75% respectively. HCV core antigen detection is quick, and easy to perform alternative to HCV RNA, and could be used as a marker of HCV viraemia for monitoring the progress of therapy.

Antiviral Agents↗

[Assessment of the living renal donor. Analysis of extra-renal pathology as a limitation for donation].

The goal of the donor evaluation is to ensure the suitability, safety and well being of the donor. In order to avoid important omissions, the evaluation of potential living kidney donors should be carried according to a protocol that includes a logical sequence of complementary explorations. Old age alone is not an absolute contraindication to donation but the evaluation should be more rigorous, because increased age may be associated with more post-operative complications after nephrectomy and renal function and long term graft survival could be shorter than the ones obtained from younger living donors. A body mass index of more than 35 kg/m2 should be an absolute contraindication to renal donation. Between 30 and 35 kg/m2 the donor evaluation should be more rigorous and it should be recommended to lose weight before nephrectomy. Hypertension is one of the most common reasons to declare a potential kidney donor unsuitable. Evidence of organ damage is an absolute contraindication to kidney donation. The donation is only reasonable when hypertension is well controlled with less than two drugs. To excluded diabetes mellitus all donors should have a fasting plasma glucose measurement. Diabetes mellitus is an absolute contraindication to living donation such as an impaired glucose tolerance or impaired fasting glucose with a family history of type 2 diabetes mellitus. Another contraindication to living donation is malignant disease, and the same standards should be adopted for cadaveric donors. The exceptions are low-grade non-melanoma skin cancer and carcinoma in situ of the uterine cervix. The presence of active infection usually precludes donation. It is very important to perform a routine test for viral infections. HIV, hepatitis B and C infection of the donor are usually a contraindication to living donor. CMV donor and recipient status should be taken into account before transplantation, and the recipients at risk for CMV disease should recieve prophylactic treatment according to the transplant unit policy.

Age Factors↗

[The living kidney donor: laparoscopy versus open surgery].

INTRODUCTION: Living renal donors are an important source of transplanted kidneys due to the number of patients on waiting list is progressively increasing. On the other side, they allow the pre-emptive kidney transplantation. With the aim of reducing donor obstacles such as pain, hospital stay or cosmetic results and in creasing the number of living donors, in 1995 Ratner performed the first laparoscopic nephrectomy (LLDN). By now, LLDN is a routine procedure in more than 200 centres worldwide. METHODS: Literature databases are searched. We have reviewed the data from our experience after performing 50 laparoscopic nephrectomies. RESULTS: Preoperative living donor assessment and contraindications to LLDN do not differ from the open approach. Results are very influenced by the surgeon's situation in the learnig curve. Operating times use to be longer in laparoscopic procedures. The overall complication rate and mortality of LLDN are the same for both of the approaches. Conversion to open-donor nephrectomy has been reported in 0-13% of cases (8% in our data). Postoperative pain and donor estimated blood loss are lower for LLDN, as well as the convalescence period. To avoid the possible negative effects of the laparoscopic technique on kidney graft function a lot of method's variations have been proposed for gaining access and harvesting the kidney, including the hand-assistance techniques, with the aim of minimizing operative time, pneumoperitoneus negative effect on graft function and warm ischemia time (WIT). The higher WIT is not related to delayed graft function or acute rejections when it is less than ten minutes. Delayed graft function does not differ in both approaches and creatinine values from the first month until the third year after transplantation show no differences in randomized studies. CONCLUSIONS: The laparoscopic approach to harvest the allograft from the living donor is a save and effective technique and has the advantage of being less invasive and allowing the donor a shorter convalescence. It has no negative effects on allograft function in the short term follow-up. Further studies are required to evaluate long term donor complications and allograft function and survival.

Age Factors↗

[Outcomes of transplantation from living renal donor].

Living donors represent 30% of our kidneys for renal transplantation. Laparoscopic nephrectomy is the best surgical procedure to obtain them due to its clear advantages such as low morbidity, less blood supply and donor time in hospital. From March 2002 to August 2004 we performed 50 laparoscopic nephrectomies for renal transplantation. Kidneys were transplanted to recipients receiving tacrolimus 0.1 mg/kg/bid, mycophenolate mofetil 1 g/bid and prednisone 0.5-1 mg/kg/day p.o 48 hours before transplantation. Mean time for surgery was 170 minutes (120-260), warm ischaemia time 3.1 minutes (1.5-10) and cold ischaemia time 1.27 hours (0.85-4). Mean bleeding was 270 cc (100-900) and donor time in hospital 5.5 days (3-9). Four cases required conversion of the laparoscopic procedure to open surgery because of bleeding. 72 hours post-transplant mean plasmatic creatinine was 170 micromol/l. None of the patients suffered delayed graft function. 18% presented acute rejection. Survival of donor and recipient was 100% at 1 year and graft survival was 94% at 1 year (kidney losses were due to acute rejection, severe acute pancreatitis and surgical problem).

Anti-Inflammatory Agents↗

Risk factors for cardiovascular disease after renal transplantation.

Cardiovascular diseases (CVD) have become the leading cause of mortality in renal transplant recipients. Well-known cardiovascular (CV) risk factors and graft dysfunction both play an important role in the development of the posttransplantation CV events. We studied 233 stable kidney transplant patients to establish the prevalence of CVD and to assess CV risk factors that can be evaluated (and modified) in daily clinical practice. While 6.2% of the patients had coronary heart disease (CHD) before the transplantation, 16% displayed at least 1 CV event posttransplantation. The most significant factors associated with CV events were as follows: gender, length of smoking, diabetes mellitus, hepatitis C virus antibodies (HCV), dyslipidemia, proteinuria, and serum creatinine levels.

Blood Pressure↗

Assessment of cyclosporine therapeutic monitoring with C2 concentrations in stable renal allograft recipients.

The optimal long-term C2 target to minimize the risk of chronic allograft nephropathy (CAN) has not yet been established in a prospective study. Furthermore, it is not known whether the target is the same in patients who also receive mycophenolate mofetil (MMF). We determined the 2-hour postdose concentration (C2) in a cohort of 65 maintenance renal transplant patients. The mean C0 level was 0.12 microg/mL and the C2 was 0.62 microg/mL. The overexposed patients are 14%. There was a good correlation between C0 and C2, and between C2 and the cyclosporine (CsA) dose. Patients receiving MMF display lower levels of C0 and C2, lower dosages of CsA, and higher levels of plasma creatinines. We did not observe significant differences on relating the level of absorption to patient age and sex, creatinine level, CsA dose, or coadministration of MMF. In conclusion, there is a low incidence of overexposed patients. C2 levels of approximately 0.6 microg/mL (and possibly may be sufficient in renal transplant patients. somewhat lower [0.5 microg/mL] in patients receiving MMF) Patients who display slow or fast absorption of CsA do not have any apparent characteristic.

Adult↗

Tacrolimus in induction immunosuppressive treatment in renal transplantation: comparison with cyclosporine.

The aim of the study was to compare the efficacy and safety of induction immunosuppression therapies based on tacrolimus or cyclosporine (CsA) in kidney transplantation. The 240 kidney allograft recipients were divided into two groups: group 1 (n=94) received tacrolimus (.01 mg/kg per day), mycophenolate mofetil (MMF, 2 g/d), and steroids (30 mg/d); and group 2 (n=146) CsA (6 mg/kg per day), MMF (2 g/d), and steroids (30 mg/d). Antilymphocyte serum was administered in cases of acute tubular necrosis. The acute rejection rate was higher among group 2 (30.6%) compared with group 1 patients (12.2%) (P=.001). There were no significant differences between the groups in terms of age, gender, body surface area, serologic virus markers (in donor and recipient), baseline creatinine levels, cause of death, HLA incompatibilities, response to acute tubular necrosis, and number of dialysis sessions. We conclude that both immunosuppressive regimens are effective and safe in kidney transplantation. The survival rates of patients and grafts were similar, but the incidence and degree of acute rejection events were reduced in group 1; this finding may forecast a decreased incidence of chronic renal allograft nephropathy.

Adrenal Cortex Hormones↗

Significance of cytomegalovirus infection in renal transplantation.

The aim of this study was to establish the relationship between vascular lesion chronic allograft nephropathy (CAN) and the presence of cytomegalovirus (CMV) in kidney transplanted patients. We studied 259 consecutive kidney transplant recipients with a minimum follow-up of 6 months; the induction immunosuppressive therapy included a calcineurin inhibitor, mycophenolate mofetil, steroids, and the use of an antilymphocyte serum if the patients developed delayed graft function. CMV early antigen detection (pp65) was performed on a weekly basis between days 30 and 90 post transplantation. Prophylactic treatment was administered in the donor +/recipient-risk group, and preemptive therapy delivered for positive antigenemia namely 3 days of intravenous [IV] gancyclovir [GCV] plus 11 days of oral therapy [in the case of infection], or 14 days of IV GCV [in the case of disease]). An acute kidney allograft rejection episode preceded CMV in 64.3% of the patients, and CMV preceded acute rejection in 35.7% of the cases. We conclude that CMV disease is an independent risk factor for CAN. CMV infection is probably associated with CAN, suggesting that the greater the viral load, the higher the risk of CAN. It may be advisable to perform universal prophylaxis to lower the viral load and CAN.

Cytomegalovirus Infections↗

Use of recombinant human erythropoietin in kidney transplant patients with stable graft function.

The purpose of this work was to determine the necessity for rhuEPO for 50 kidney transplant patients with stable graft function. We analyzed the red cell series, blood pressure, renal function, anthropometric data of the donor and recipient, proteinuria, and relationship with other factors, including immunosuppressants, angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB). The patients were divided into three groups depending on renal function: group A (with plasma creatinine <150 micromol/L), group B (151-250 micromol/L), and group C (>250 micromol/L). All patients were studied for 1 year. Erythropoietin use did not affect renal function, proteinuria or number of antihypertensive drugs group. The degree of renal dysfunction determined the time necessary to reach an adequate hemoglobin level (>12 g/L) and and the mean dose of weekly rhuEPO needed. The use of ACE inhibitors or ARBs increased the rhuEPO requirements in each group.

Angiotensin-Converting Enzyme Inhibitors↗